The Budget Crisis, Universities, and Key Opinion Leaders

Everyone knows that state budgets across the United States are in a crunch. All state-supported universities are looking for sources of income outside of taxpayer funds. As state legislatures look to cut money, many state universities are in for a big budget hit. So if the state is going to pony up less money, how can a university survive...?

Perhaps by seeking to entice industry funding. Set up a few clinical trials and see what happens. There is nothing inherently wrong about university faculty working on industry-sponsored research. In an ideal world, all goes according to plan and all benefit from such collaboration. Universities love industry collaboration because it brings in good money. Researchers like to collaborate with industry for some altruistic motives, such as receiving funding to work on investigating treatments that might hopefully bring about better lives for people struggling with various ailments. Because receiving funding makes the university
administration happy, it also makes life at a university medical center much more pleasant for those who bring in the bucks.

But how do things really work? Sometimes, they go well. But there are also nondisclosure agreements, in which an "independent" academic researcher gives away any right to discuss the data from clinical trials that he/she is working on unless approval is given by industry. As Graham Emslie, key opinion leader in the field of child psychiatry, can attest to, there are certainly many cases where negative results were found for a drug, but the negative data were buried to avoid any untoward publicity. Academics often farm out their writing of joint work with industry to ghostwriters who spin the final product to pimp a product rather than accurately describe the results. As regular readers know, this is just the tip of the iceberg.

If academics are willing to be oversee industry-sponsored research, have substantial input into writing the final presentation of the results, and actually review the data from these joint ventures with industry, then academic-industry collaboration can be fruitful. However, if academics are simply used to recruit patients for clinical trials, stamp their names on papers consisting of data with which they are entirely unfamiliar, and are complicit in hiding negative data, then the current sad state of affairs will continue unabated.

Given the current financial situation, universities will be encouraging faculty very strongly to get external funding for their work, and we can only hope that academics will behave responsibly when such collaborations occur.

Smoke and SHHHHHHHHHHHH!

Alan Finder at the New York Times  has, pardon the bad pun, a smokin' good story about entangled relationships, cigarettes, secrecy and Virginia Commonwealth University (VCU).  To what do I refer?  VCU signed a contract with Philip Morris to conduct research, but the catch is that there is a mega-gag order.  Professors aren't allowed to discuss or publish their results without the permission of (guess...) Philip Morris.  If someone (say, a journalist) asks someone at the university about this agreement, university officials are required to decline comment.  The inquiry is then passed along to the company.  Apparently intellectual property rights emerging from any discoveries from such research belong to Philip Morris, not the university researchers.  Until this story broke, it appears that the vast majority of faculty and students were unaware of this contract, maybe due to its potential for negative public relations.

What does VCU have to say?

“There is restrictive language in here,” said Francis L. Macrina, Virginia Commonwealth’s vice president for research, who acknowledged that many of the provisions violated the university’s guidelines for industry-sponsored research. “In the end, it was language we thought we could agree to. It’s a balancing act.”

Oh, that's okay then.  Just because you are Philip Morris's hush-hush scientific whore, it's not a big deal.  It's a "balancing act," which roughly translates to "We'll do anything for a buck."  

But then...

Rick Solana, the senior vice president for research and technology, said university scientists were studying how to identify early warning signs of pulmonary disease, and how to reduce nitrogen and phosphorus drained into rivers from processing tobacco leaves. Dr. Solana also said the contract represented a new focus on developing tobacco products with reduced risks, a shift in strategy in underwriting university research that requires more confidentiality to protect the corporation’s intellectual property rights. And he said Philip Morris had similar arrangements with other universities — although he declined to say how many or which ones.

Imagine that, other universities taking money from tobacco.  All in the name of good science, naturally.  The contract forbids faculty from publishing results without PM's permission, which is a direct violation of VCU's guidelines for industry-faculty collaboration.  But, again, when taking in buckets o' money, all is fair game.  Hey, keep cutting public funding for universities and see if we can make researchers yet more dependent on pharma, tobacco, and whomever else waves the dolla dolla bill.  

Much more analysis available here.

"Not Much Money," KOLs, and Child Bipolar Disorder

Intro. A few months ago, I wrote about key opinion leaders (KOLs) in psychiatry arguing that we shouldn't be making such a big deal about their payments from drug companies. After all, they were just receiving chump change. At the time, my motivation was spurred by a great piece in the New York Times on the issue of physicians receiving payments from drug companies. Physicians are often paid to become "key opinion leaders," aka salespeople. Often possessing academic positions, these KOLs give speeches to fellow physicians in which they extol the virtues of a drug in exchange for cash. Of course, physicians might be leery if a sales representative was discussing the latest wonder drug, so using an "independent" physician uses a basic marketing trick, the third-party technique, in order to give the marketing message a veneer of credibility. For the past few years, KOLs have been lighting up the upscale restaurant scene across the nation, discussing the benefits of atypical antipsychotic (er, broad spectrum psychotropic) treatment for a wide variety of ills. From schizophrenia to bipolar disorder to anxiety to well, pretty much anything you can imagine, antipsychotics are the treatment du jour.

"I don't make much." One KOL in the wonderful world of atypicals has been Melissa DelBello. In particular, her specialty is children with bipolar disorder. I've previously stated my beef with the child bipolar paradigm and I'll discuss a couple of my contentions a bit later in the post. DelBello has been involved in research regarding the treatment of child bipolar disorder (not saying I necessarily agree with the term; just using it because she used it). As a KOL, DelBello has given talks supported by AstraZeneca, manufacturer of Seroquel. As for her reimbursement for such talks, she said "Trust me. I don't make much."

Here is what a little investigation from Senator Charles Grassley uncovered regarding DelBello's definition of "not much" money.

Here is where it gets interesting. After Dr. DelBello released her study, Astra Zeneca began hiring her to give several sponsored talks. Another doctor told The New York Times he was persuaded to start prescribing drugs [Page: S10722] such as Seroquel after listening to Dr. DelBello. But when the reporter from the New York Times asked Dr. DelBello how much money she got from Astra Zeneca, she told the paper: ``Trust me. I don't make much.''

Well, I decided to find out how much, and I went directly to the University of Cincinnati who, by the way, has been extremely cooperative, helpful, and responsive. Soon I figured out just how much ``not that much'' money is. Dr. DelBello's study, which helped put Seroquel on the map, was published in 2002. That next year, she got more money than she has ever received from the pharmaceutical companies--at least that is what the documents that I have say.

In 2003, Astra Zeneca alone paid her a little over $100,000 for lectures, consulting fees, travel expenses, and service on advisory boards. In 2004, Astra Zeneca paid her over $80,000 for the same services.

So, if I have this correct, $180k over two years is "not much money." Hey, this is quite similar to a response from another moonlighting entrepreneur with a license to practice medicine. To quote from the New York Times...

The psychiatrist receiving the most from drug companies was Dr. Annette M. Smick, who lives outside Rochester, Minn., and was paid more than $689,000 by drug makers from 1998 to 2004. At one point Dr. Smick was doing so many sponsored talks that “it was hard for me to find time to see patients in my clinical practice,” she said.

“I was providing an educational benefit, and I like teaching,” Dr. Smick said.

Right. The companies provide you with the slides and the key marketing points, and you call yourself an "educator." Um, doesn't that actually make you a marketer? And the clincher: Who has time for patients in clinical practice when you are off stumping for the hot drug of the week?

The KOL-Pharma Marriage: For all I know, Dr. DelBello is a great human being. I disagree with her a great deal on the child bipolar thing, but there are certainly many very bright and reasonable people who see things differently than myself. Personally, I have difficulty seeing the child bipolar bandwagon as anything other than a massive campaign to re-brand a broad spectrum of unruly behavior under one heading that can be used to call out for antipsychotic treatment. Researchers in the area of child bipolar perceive that scientific progress is being made because they have "discovered" a condition that affects millions of youth. Big Pharma loves it because, conveniently, they can treat this newfound condition with their cash cow atypical antipsychotics. And the marriage between child bipolar researchers and Big Pharma becomes even tighter through the well-paying speaking gigs in which KOLs pimp atypicals as the treatment for child bipolar, a condition that was considered quite rare until KOLs and Pharma "educated" us about this "neglected and undertreated serious medical condition."

Taking large payments then writing them off as "not much" just adds another brick to the wall of conflicted interests that dominates medicine these days. The physician-marketer (aka KOL) can perhaps take great pride in the rate of treatment for child bipolar expanding by perhaps 4000% of late. In fact, the spread of atypical antipsychotics for children, the elderly, and everyone else is such good news that I think KOLs should be up for some sort of marketing award. Go Team Seroquel! Viva Zyprexa! Rock on Geodon Crew! Gimme an I-N-V-E-G-A! Pimp that Abilify!

Believe it or not, I'm not against industry-academic collaboration. But I am against industry-academic corruption. When there are no checks and balances on a system, one should not be surprised when it is subverted by a combination of power and money. When academics turn into industry spokespeople, or become information launderers, or become medal winners in the conflict of interest department, why on Earth should we simply trust them as if they had no skin in the game?

Peer Review, GSK, Cash, and Limp Noodles

Stephanie Saul has a quite interesting story in the New York Times about a peer-reviewer who really dropped the ball.

A key member of the Senate said Wednesday that a prominent diabetes expert leaked an unpublished and confidential medical journal article to GlaxoSmithKline last year, tipping the company to the imminent publication of safety questions involving the company’s diabetes drug Avandia.

The doctor, Steven M. Haffner of the University of Texas Health Science Center in San Antonio, faxed the article to the drug maker after agreeing to read it as part of the peer-review process for the New England Journal of Medicine, according to a statement Wednesday by Senator Charles E. Grassley...

An article on the matter that was published online Wednesday by the journal Nature quoted Dr. Haffner. “Why I sent it is a mystery,” the quote says. “I don’t really understand it. I wasn’t feeling well. It was bad judgment."

OK, I have to give Haffner credit for admitting his error. However, "I wasn't feeling well" -- not a great excuse. According to a GSK spokesperson, Haffner sent the article to GSK for "advice from experienced statisticians." The spokesperson denied that GSK provided any feedback to Haffner. Um, couldn't Haffner have found a statistician who did not work for GSK? As you might guess, this type of behavior is a no-no; the New England Journal of Medicine (as well as virtually all journals) has a policy where peer reviewers are not to share the content of papers under peer review with others.

Why did Haffner go to GSK? Well, here's one possible reason...

Dr. Haffner has previously disclosed that he has conducted research and served as a paid speaker for Glaxo. [Iowa Senator] Mr. Grassley said that Dr. Haffner had received $75,000 in consulting and speaking fees from GlaxoSmithKline since 1999

Maybe it was his relationship with GSK, maybe not. Haffner is apparently not a fan of medical journals, as can be seen in the quote below:

“The three major medical journals are becoming more like British tabloid newspapers — all they lack is a bare-chested woman on page 3,"

Apparently if they changed their peer review process to include submitting papers critical of industry for "objective" peer review by precisely the companies they are criticizing, that would help to de-tabloid the journals??

At the end of the article, Saul notes a case of limp noodle punishment for a similar violation...

Last year the New England Journal sanctioned another physician, Dr. Martin B. Leon, for commenting on a study before its publication. Dr. Leon, who was a reviewer of a journal article on the effectiveness of heart stents, disclosed at a medical conference that the study’s findings were negative before the article appeared. As a result, the journal barred Dr. Leon from reviewing articles for five years, and said he could not submit commentary for publication in the journal during that period.

Oh, THAT will teach him a lesson! He can't spend his free time reviewing articles for a journal. Ouch, that might leave a mark. And he can't publish an editorial for five years in one journal?? With hundreds of other journals to choose from, how will he survive? See some interesting comments on the Leon case here.

Hat Tip: Furious Seasons

Bribing Physicians: Where My Money At?

An utterly fascinating article in the Wall Street Journal by Vanessa Fuhrmans notes that insurers are moving to bribe doctors for prescribing generics. Snippet below, but you really should read the whole article.

Health plans are drawing scrutiny for offering financial incentives to entice doctors to prescribe cheaper generic medicines, including paying doctors $100 each time they switch a patient from a brand-name drug.

Pharmaceutical companies have long gone to great lengths to try to get doctors to prescribe their brand-name pills. They spend billions of dollars, plying physicians with samples, educational lunches and speaker fees. But as the patents for a growing number of blockbuster medicines expire, some health insurers are trying to trump those perks with bonuses or higher reimbursements for writing more generic prescriptions.

The idea, health plans say, is to save everyone -- patients, employers and insurers -- money. And many doctors argue that it's only right to reimburse them for spending time evaluating whether a cheaper generic alternative is better or as good for a patient.

But the more aggressive approaches, such as cash rewards for each patient switched from a given list of drugs, are coming under fire for injecting financial incentives into what some patient advocates and legislators say should be a purely medical decision. Medical societies are also concerned that such rewards may put doctors in the ethically questionable position of taking a payment that patients know nothing about.

There is little doubt that many newer medications offer little to no benefit over generics and this site and others have frequently noted that prescription practices often appear quite irrational. In psychiatry, for example, the movement to place everyone on Depakote and/or atypical antipsychotics for treating bipolar disorder was a marketing miracle considering that the evidence base never showed superior efficacy relative to lithium. The same story goes for treating schizophrenia with atypical antipsychotics over conventional antipsychotics (as well as ignoring psychosocial interventions) based on a set of obviously flawed studies. Or treating depression with newer antidepressants rather than generics or (especially) with psychotherapy, which is generally linked to better long-term outcomes.

Of course, as has been documented here and many other places, we know that Big Pharma utilizes a variety of methods to ensure that physicians prescribe newer drugs, even if such prescriptions are irrational. If we just consider this as a battle of mega-industries who want to maximize their profits (Pharma vs. Insurance), then maybe this is the unfettered free market at its best?

On one hand, we have Pharma using a variety of tricks, including: buying meals, providing all sorts of gifts, infomercials disguised as medical education, tricky statistics, burying negative findings, and just being sooooo good looking, and on the other we now have insurers providing kickbacks to doctors for prescribing generics. Both pharma and insurers are attempting to influence prescribing through methods far outside of providing objective medical information to physicians. I know that some favor a pure free market approach and if so, then I suppose that this is just the latest and greatest maneuver in which companies attempt to pimp their wares (Pharma) or buy physician loyalty to a different set of products (Insurers).

As for the patients, um, who is looking out for their interests? I realize that physicians genuinely want their patients to improve (well, maybe not this one), but is a system of competing interests trying to irrationally manipulate physicians' prescribing practices really the best way to ensure patient wellness?

By the way, how much $$$ could insurers save? See below.

Hat Tip: PharmaGossip

To sum up the current state of affairs in four words: Dolla Dolla Bill Y'All